The present invention relates to the revelation of genes involved in the molecular pathways of tumor suppression and/or resistance to viruses.
1. Field of the Invention
The present invention has been made possible by the isolation of cDNA corresponding to messenger RNAs expressed or repressed during tumor suppression and/or during the process of apoptosis induced by the p53 suppressor gene.
2. Description of the Art
One of the most important suppressor genes involved in apoptosis is the p53 gene. When functioning normally, this gene controls cell growth and the process of apoptosis; in particular, it is this gene which blocks cell growth and which must induce the apoptotic process in order to avoid the development of a cancer. It has thus been demonstrated that mice nullizygous for p53 are much more sensitive to the formation of tumors. The fact that, in cancers, the p53 gene is very often modified and leads to the production of proteins incapable of vehicling the message of apoptosis has also been demonstrated.
It is this particularity which has been used in the context of the present invention.
Specifically, the present invention is based on the observation that it is not possible, or at least that it appears to be very difficult, to set up a direct substitution therapy when there is dysfunctioning of the p53 gene. Specifically, p53 which is mutated, as it is in cancer, will annul the physiological effect of normal p53.
It has therefore been necessary to abandon, at least initially, the idea of a substitution therapy acting directly on p53.
The present invention has, therefore, endeavored to study the genes located upstream and downstream of p53 in order to bypass the difficulty mentioned above.
In order to isolate the genes activated or inhibited by normal p53 (wild-type p53), an overall combing of gene expression has been carried out in a malignant line (K562) and a derived cell (KS) in which the malignant phenotype is suppressed, more particularly in a cell expressing p53 which is functionally normal (KS) and in a cell not expressing p53 (K562). Comparison of the genes expressed (messenger RNAs expressed in the two types of cell) has made it possible to reveal genes expressed differentially, i.e. expressed in one of the cells whereas they are not expressed in the other (the genes may be activated or inhibited).
It is easily deduced therefrom that these genes are involved in the cancerization process, in one case by their absence and, in the other case, by their presence.
The method used for this differential study is the method described in 1992 by Liang and Pardee (Differential display of eukaryotic mRNA by means of a polymerase chain reaction).